Abstract: Objective To investigate the impact of femoral prosthesis malposition on internal structural strain in unicompartmental knee arthroplasty for osteoporotic knees. Methods A normal bone knee joint model was constructed based on imaging studies (CT, magnetic resonance imaging) of healthy volunteers, and an osteoporotic knee joint model was constructed by altering the elastic modulus. Finite element models of femoral prosthesis malposition in unicompartmental knee arthroplasty were then established for both normal bone and osteoporotic groups. A vertical static load of 1, 000 N was applied to both models, and the peak strain values and distributions were observed in the medial compartment structures (polyethylene gasket, cancellous bone under tibial prosthesis) and lateral compartment structures (meniscus, tibial cartilage) at various malposition angles of the femoral prosthesis. Results The peak strain values of the polyethylene gasket, cancellous bone under tibial prosthesis, meniscus, and tibial cartilage in the osteoporotic group were higher than those in the normal bone group at different varus and valgus angles. In the osteoporotic group, the peak strain values of the polyethylene gasket and cancellous bone under tibial prosthesis increased with the increase in femoral prosthesis malposition angle, with a greater increase at valgus angles than at varus angles. Similarly, the peak strain values of the meniscus and tibial cartilage increased with the increase in femoral prosthesis malposition angle, but the increase was greater at varus angles than at valgus angles. The strain concentration area of the polyethylene gasket was located in a circular-like area where the femoral prosthesis contacted the gasket, the strain concentration area of the cancellous bone was mainly located in the posterolateral region, the strain concentration area of the meniscus was located near the anterior horn, and the strain concentration area of the tibial cartilage was mainly located in the middle near the intercondylar eminence. Conclusion Osteoporosis may adversely affect the strain on internal structures of the knee joint after unicompartmental knee arthroplasty. Varus malposition of the femoral prosthesis may exacerbate the progression of osteoarthritis in the contralateral compartment (lateral compartment), while valgus malposition may increase the risk of prosthesis loosening and revision surgery.